Primary Tumor Location Research Articles

18F-FAPI-42 PET/CT and 18F-FDG PET/CT in Patients with Malignant Digestive System Neoplasms: A Head-to-Head Comparative Study.

Radionuclide-labeled fibroblast activation protein inhibitor (FAPI) is an emerging tumor tracer. We sought to assess the uptake and diagnostic performance of 18F-FAPI-42 PET/CT compared with simultaneous 2-deoxy-2[18F]fluoro-D-glucose (18F-FDG) PET/CT in primary and metastatic lesions in patients with malignant digestive system neoplasms and to determine the potential clinical benefit. Forty-two patients (men = 30, women = 12, mean age = 56.71 ± 13.26years) who underwent 18F-FDG PET/CT and 18F-FAPI-42 PET/CT simultaneously for diagnosis, staging, and restaging were enrolled. Quantitative data, including standardized uptake value (SUV), tumor-to-liver ratio (TLR), and tumor-to-blood pool ratio (TBR), were analyzed. Two independent readers performed a visual assessment of lesion number and location on PET/CT images. Interobserver agreement between two examinations was calculated using Cohen's kappa (κ). Primary tumor locations included the liver (n = 20), stomach (n = 9), pancreas (n = 5), and intestine (n = 10). More intense 18F-FAPI-42 uptake and higher tumor-to-background contrast were detected in most primary and metastatic lesions compared with 18F-FDG, contributing to improved diagnostic accuracy ranging from 95.24% to 100%. Moreover, additional lesions showing 18F-FAPI-42 uptake in primary, locoregional and distant metastatic lesions were visualized, especially in multiple liver and peritoneal metastases. Patient-based interobserver agreement varied from moderate to strong, with suboptimal outcomes observed in primary tumors (κ = 0.441, P = 0.01) and preferable results derived from metastatic liver and bone lesions (κ = 1 and 0.896, both P < 0.01). 18F-FAPI-42 PET/CT resulted in modified treatment strategies for 40.48% (17/42) of patients, while 18F-FDG PET/CT led to altered therapeutic regimens in only 4.8% (2/42) of patients. In selected patients with malignant digestive system neoplasms, our study shows that 18F-FAPI-42 PET/CT is a promising alternative for assessing primary tumors and metastases and aiding staging, restaging, and decision-making, with higher uptake and better lesion visualization compared with 18F-FDG. Additionally, it may shed light into the treatment selection and response assessment for FAP-targeted therapy or immunotherapy.

Neo-adjuvant FOLFOX with and without panitumumab for patients with KRAS-wt locally advanced colon cancer: results following an extended biomarker panel on the FOxTROT Trial embedded phase II population.

The FOxTROT trial has reported advantages of neoadjuvant chemotherapy (NAC) in locally advanced colon cancer (LACC). Here we present results of the embedded randomized phase II trial testing the addition of panitumumab to neoadjuvant FOLFOX compared with FOLFOX alone in RAS and BRAF-wild-type patients and with biomarker hyperselction. Patients had operable, CT-predicted stage T3-4, N0-2, M0 colon adenocarcinoma. KRAS-wt pts allocated to NAC could optionally be sub-randomized 1:1 to FOLFOX ± panitumumab during the pre-operative phase. RAS/BRAF were tested by NGS; EREG/AREG by RNAseq. Primary endpoint is time to recurrence (TTR) in RAS/BRAF-wt patients; secondary endpoints include safety, histological downstaging, disease-free survival (DFS), colon cancer-specific survival (CCSS), overall survival (OS), and impact of primary tumor location and EREG/AREG. In total 269 KRAS-wt patients were enrolled into the embedded phase II trial. Extended RAS/BRAF data were available for 232 (83%) patients; 22/232(9.5%) were RAS-mutant; 41/210(20%) were BRAF-mutant. Median follow up was 42 months. In 169 RAS/BRAF-wt patients there was a trend towards reduced recurrences with FOLFOX plus panitumumab compared with FOLFOX (12% vs 21%, HR=0.51, p=0.09); significant improvements were seen for DFS, CCSS and OS. Within the hyperselected EREG/AREG high group, there was significant reduction in recurrences with panitumumab. Panitumumab was not associated with increased pathological regression of the primary tumor (TRG 1-3 16% vs 22%,p=0.27). FOLFOX plus panitumumab was associated with higher rates of grade 3 diarrhoea (8% vs 3%,) and rash (22% vs 2%). This exploratory analysis from a randomized phase II study shows a non-significant improvement in TTR from the addition of neoadjuvant panitumumab to peri-operative FOLFOX in RAS/BRAF-wt LACC. Hyperselection with EREG/AREG status was associated with increased efficacy. A dedicated prospective trial within a biomarker selected population is under development. ISRCTN87163246.

Location of Primary Tumor Impacts Survival After Pulmonary Metastasectomy for Colorectal Cancer.

The benefit of pulmonary metastasectomy (PM) in patients with colorectal cancer (CRC) with isolated lung metastases remains unclear and failure to separate colon from rectal cancer may contribute. Utilizing a large national database, we investigate whether PM is associated with survival benefits in patients presenting with CRC with synchronous lung metastases based upon primary tumor location. The Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 was queried to identify patients with stage IV CRC with isolated synchronous lung metastases at initial diagnosis. These patients were restricted to include only those where the location of the primary tumor being either colon or rectum could be conclusively identified, and the primary site was resected. SEER-linked Medicare claims were also queried to identify cases of PM that were not adequately recorded in SEER alone. Patients were then analyzed using Kaplan-Meier (K-M) methods and multivariate analysis was performed to identify variables associated with overall survival (OS). From the SEER database 185,871 metastatic CRC patients were identified. Only 588 had isolated synchronous lung metastases, with 441 with colon cancer and 147 with rectal cancer. PM was performed in 15.3% (n=90) with two-thirds being colon cancer. Univariate K-M demonstrated worse OS for rectal cancer compared to colon cancer, which remained significant on multivariate analysis. OS is associated with site of primary CRC in patients undergoing PM. Distinct mutational and molecular characteristics differences between colon and rectal cancer may explain these findings and is an area for future research.

Prevalence and Risk Factors of Oropharyngeal Dysphagia in Newly Diagnosed Head-and-Neck Cancer Patients.

Head-and-neck cancer (HNC) can cause oropharyngeal dysphagia (OD). Early identification of OD in newly diagnosed HNC patients is important to better prepare patients for their cancer treatment trajectory. The aim of this study is (1) to assess the prevalence of OD in HNC patients within three weeks before the start of cancer treatment and (2) to investigate which demographic and oncological characteristics may be risk factors associated with the risk of OD at baseline. Patients (N = 225) completed the Eating Assessment Tool-10 (EAT-10) and Short Nutritional Assessment Questionnaire (SNAQ). Logistic regression analysis was conducted to examine the association between OD versus demographic and oncological characteristics. A total of 21.3% (proportion 0.213; 95% CI 0.163-0.274) of the patients were at risk for OD. After correction for age, Charlson Comorbidity Index (CCI) grade, and primary tumor location, a significant association was found between advanced-stage cancer versus the risk of OD. Additionally, post hoc analysis revealed a significant association between the risk of malnutrition versus the risk of OD. Approximately one-fifth of all newly diagnosed HNC patients are at risk of OD, with advanced-stage cancer and malnutrition emerging as significant risk factors of OD. These findings empower health professionals toward more effective screening and management of a patient's risk profile before the start of HNC treatment.

Design Principles of an Engineered Metastatic Niche for Monitoring of Cancer Progression.

Across many types of cancer, metastatic disease is associated with a substantial decrease in 5-year survival rates relative to only a localized primary tumor. Many patients self-report metastatic disease due to disruption of normal organ or tissue function, and earlier detection could enable treatment with a lower burden of disease. We have previously reported a subcutaneous biomaterial implant for early detection by serving as an engineered metastatic niche, which has been reported to recruit tumor cells before colonization of solid organs. In this report, we investigated the design principles of the scaffold and defined the conditions for use in disease detection. Using the metastatic 4T1 triple-negative breast cancer model, we identified that a porous structure was essential to capture tumor and immune cells. Scaffolds of multiple diameters were investigated for their ability to serve as a metastatic niche, with a porous scaffold with a diameter as small as 2 mm identifying disease accurately. Additionally, scaffolds that had been in vivo for 1-5 weeks were able to identify disease accurately. Finally, the sensitivity of the scaffold relative to liquid biopsies was analyzed, with scaffolds accurately detecting disease at earlier time points than liquid biopsy. Collectively, these studies inform the design principles and use conditions for porous scaffolds to detect metastatic disease.

Ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line oxaliplatin-based chemotherapy in patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer (ARMANI): a randomised, open-label, multicentre, phase 3 trial.

Paclitaxel plus ramucirumab is recommended as a second-line treatment regimen in patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer. We aimed to assess whether switch maintenance or early second-line therapy with paclitaxel plus ramucirumab improved outcomes compared with continuation of oxaliplatin and fluoropyrimidine doublet chemotherapy as a first-line strategy. ARMANI was a multicentre, open-label, randomised, phase 3 trial done in 31 hospitals in Italy. We enrolled patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1 and locally advanced unresectable or metastatic HER2-negative gastric or gastro-oesophageal junction cancer, who had disease control after 3 months of FOLFOX (leucovorin, fluorouracil, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin). Patients were randomly assigned (1:1) to either paclitaxel 80 mg/m2 on days 1, 8, and 15 plus ramucirumab at 8 mg/kg on days 1 and 15 every 28 days intravenously (switch maintenance group) or continuation of oxaliplatin-based doublet chemotherapy (FOLFOX or CAPOX) for an additional 12 weeks, followed by fluoropyrimidine monotherapy maintenance (control group). Randomisation was stratified by previous gastrectomy (no vs yes), peritoneal carcinomatosis (yes vs no), and primary tumour location (gastro-oesophageal junction vs gastric). Treatment group allocation was done using a web-based system with a minimisation algorithm implementing a random component. The primary endpoint was progression-free survival, analysed on an intention-to-treat basis. The safety population included patients who received at least one dose of the study treatment. This study is registered with ClinicalTrials.gov, NCT02934464, and is complete. Between Jan 1, 2017, and Oct 2, 2023, 280 patients were randomly assigned to receive paclitaxel plus ramucirumab (switch maintenance group; n=144) or to continue FOLFOX or CAPOX (control group; n=136). All patients were White. 180 (64%) of 280 patients were male and 100 (36%) were female. At a median follow-up of 43·7 months (IQR 24·0-57·9), 253 (90%) of 280 patients had a progression-free survival event: 131 (91%) of 144 patients in the switch maintenance group and 122 (90%) of 136 patients in the control group. Median progression-free survival was 6·6 months (95% CI 5·9-7·8) in the switch maintenance group and 3·5 months (2·8-4·2) in the control group (HR 0·61, 95% CI 0·48-0·79; p=0·0002). The assumption of proportional hazards was violated; in an analysis of 24-month restricted mean survival time, restricted mean progression-free survival was 8·8 months (95% CI 7·7-9·9) in the switch maintenance group and 6·1 months (5·0-7·2) in the control group (p=0·0010). The most frequent grade 3-4 treatment-related adverse events were neutropenia (37 [26%] patients in the switch maintenance group vs 13 [10%] patients in the control group), peripheral neuropathy (eight [6%] vs nine [7%]) and arterial hypertension (nine [6%] vs none). Serious adverse events occurred in 28 (20%) of 141 patients in the experimental group and 15 (11%) of 135 patients in the control group; these events were treatment-related in two (1%) patients in the switch maintenance group (pulmonary embolism) and two (1%) patients in the control group (mucositis and anaemia). No treatment-related deaths occurred. Paclitaxel and ramucirumab switch maintenance could be a potential treatment strategy in patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer who are not eligible for immunotherapy or targeted agents. Partly funded by Eli Lilly.

Advancements in prognostic factors and survival outcomes following pulmonary metastasectomy for head and neck cancers.

Surgical treatment of lung metastases originating from head and neck tumors has shown favorable outcomes with low incidence of complications and mortality. This study aims to investigate survival and prognostic factors following pulmonary metastasectomy for head and neck cancers. A comprehensive review of the literature was conducted through the Medline database, focusing on English-language studies related to surgical treatment of lung metastases from head and neck cancers. Lung metastases occur frequently in patients with head and neck tumors, significantly impacting overall survival. Multidisciplinary assessment is crucial in determining treatment strategies, with notable improvements in survival rates observed over recent decades. Various studies have reported survival outcomes and prognostic factors, highlighting the significance of factors such as primary tumor localization, histology, and completeness of resection. Pulmonary metastasectomy with curative intent for head and neck cancers is a safe and effective treatment option that can prolong survival in selected patients.

Fluorescence-Guided Surgery Using 5-Aminolevulinic Acid/Protoporphyrin IX in Brain Metastases

BACKGROUND AND OBJECTIVES: The purpose of this systematic review was to provide a comprehensive overview of the available literature on 5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PpIX) fluorescence-guided surgery (FGS) for the resection of brain metastases (BMs). METHODS: A comprehensive search of the PubMed database for literature on 5-ALA use in BMs surgery was performed. For inclusion, BMs studies had to have data on the observed intraoperative fluorescence available. Additional data categories included the number of metastatic tumors, 5-ALA dosage and timing, the imaging system (eg, microscope) used, imaging wavelength(s), fluorescence grading (“simple” and “detailed”), fluorescence consistency (heterogeneous vs homogeneous), intracranial tumor location, metastatic primary tumor location, and extent of resection, among others. RESULTS: Twenty-three articles published between 2007 and 2022 met the inclusion criteria. These studies comprised 1709 total patients; 870 metastatic samples were collected from 855 patients with 377 (43.3%) fluorescence-negative and 493 (56.7%) fluorescence-positive samples. The pooled overall prevalence of fluorescence-positive metastatic lesions was 66% (95% CI 55%-75%; I2 = 85%, P &lt; .01). The fluorescence grading was as follows: (a) simple fluorescence (n = 599): 295 (49.3%) fluorescence-negative and 304 (50.8%) fluorescence-positive samples and (b) detailed fluorescence (n = 271): 82 (30.3%) no fluorescence, 107 (39.5%) weak fluorescence, and 82 (30.3%) strong fluorescence. A total of 764 lesions had primary tumor site data available: 702 lesions had fluorescence data with 384 (54.7%) fluorescence-positive samples. CONCLUSION: FGS using 5-ALA/PpIX in BMs demonstrates varying benefits as an adjunct for maximizing the extent of resection. Thus, preoperative knowledge of the primary tumors' origin may inform surgeons regarding the potential utility of 5-ALA/PpIX for FGS management of BMs.

The risk and distribution of second primary cancers according to subsite of primary stomach cancer: a retrospective cohort population-based study.

The development of second primary cancers (SPCs) following a diagnosis of stomach cancer presents a significant clinical challenge, with varying risks depending on the anatomic subsite of the primary tumor, patient demographics, and treatment modalities. This study aims to assess the risk of SPCs in stomach cancer survivors, focusing on differences across anatomic subsites, sex, age, and treatment periods. The authors conducted a retrospective cohort study using data from stomach cancer patients, analyzing the incidence of SPCs based on the anatomic location of the primary tumor, with stratifications by sex, age, latency period, and year of diagnosis. Standardized incidence ratios (SIRs) were calculated to compare the observed SPC rates with those expected in the general population. Elevated stomach SPC risk was observed across most anatomic subsites, particularly in the body (SIR 8.84) and fundus (SIR 7.34). Females exhibited higher SIRs compared to males, especially in the fundus (SIR 13.33 for females vs. 4.55 for males). Younger patients (<50 years) had significantly higher SPC risks, particularly for cancers originating in the fundus (SIR 49.56). Notably, patients diagnosed after 2010 showed the highest SIRs, indicating a potential impact of advances in diagnostic and therapeutic modalities. Nonstomach SPCs, including colorectal, lung, and thyroid cancers, were significantly elevated, with distinct patterns based on the primary tumor site. The study highlights the critical role of primary tumor location, sex, age, and treatment era in determining SPC risk in stomach cancer survivors. These findings underscore the need for tailored surveillance strategies to manage long-term cancer risks in this population.

Use of inpatient systemic chemotherapy and/or radiotherapy and related predictive factors, healthcare resource utilization, and direct hospitalization costs for metastatic urothelial cancer: findings from a real-world retrospective observational study derived from the national hospital discharge claims database in Italy

BackgroundRecent real-world studies revealed high proportions of patients with metastatic urothelial cancer (mUC) do not receive any systemic therapy. This study describes the demographics, clinical characteristics, treatment rate and related predictive factors, healthcare resource utilization, and direct medical costs of patients with mUC receiving systemic therapy (or not) in the inpatient setting in Italy.MethodsThis retrospective observational study used the national hospital discharge database (Scheda di Dimissione Ospedaliera) to describe incident adult (≥ 18 years) patients with a first hospitalization for mUC (index) from 2017-2018, identified by a combination of ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification), medical procedure, and diagnosis-related group codes. A model was fitted to identify factors associated with receiving inpatient chemotherapy and/or radiotherapy.ResultsOf 3674 patients with mUC identified, 1014 (27.6%) were treated with inpatient chemotherapy and/or radiotherapy and 2660 (72.4%) were not treated. The median age at index was 71 and 78 years for treated and untreated patients, and the mean (SD) Charlson Comorbidity Index (CCI) score was 0.3 (0.8) and 0.6 (1.1), respectively. Primary tumor location was the bladder in 87.2% of patients. Cardiovascular disease and renal function impairment were more prevalent in untreated (22.6% and 13.2%) vs treated (16.7% and 7.8%) patients. Older age (odds ratio [p-value]) (0.94 [< 0.001]), female sex (0.82 [0.035]), and higher CCI score (0.82 [< 0.001]) were all associated with a lower likelihood of receiving inpatient systemic treatment. The first year was the costliest: estimated national projected costs during the 36-month follow-up from first hospitalization for mUC were €34.3 million (95% CI, €30.3-€60.0 million) and €31.8 million (95% CI, €28.1-€56.0 million) when estimated after 1 year.ConclusionsOur findings indicate a low rate of inpatient systemic therapy for patients with mUC in Italy (driven by older age, female sex, and high comorbidity burden), with a large economic burden despite a high nontreatment rate. Although this study provides a partial capture of the treatment pathway in Italy, the results are consistent with other European studies with similar designs and highlight the need to better identify the reasons for not administering inpatient systemic chemotherapy and/or radiotherapy.

Impact of colorectal cancer screening by primary tumor location in a real-world setting in Japan.

The objective of this retrospective observational study was to investigate the impact of fecal occult blood test (FOBT) as colorectal cancer (CRC) screening by primary tumor location. We compared the risk of requiring treatment for advanced disease and total medical costs per patient between CRC patients who underwent FOBT within 1 year before initial treatment for CRC and those who did not, using the JMDC Claims database, large-scale health insurance claims and checkup data in Japan. Treatment for advanced disease was defined as (1) nonendoscopic therapy or (2) chemotherapy or radiotherapy, performed during the follow-up period. A total of 1194 participants with CRC (right-sided, 22.2%; left-sided, 60.4%) who initiated treatment between 2010 and 2016 and underwent health checkups within 1 year before the initial treatment were enrolled and followed up for an average of 46.1 months. A significantly lowered risk ratio (RR) of chemotherapy or radiotherapy and total medical costs were observed in FOBT group for left-sided CRC [RR = 0.78 (95% confidence interval, 0.63-0.97), mean and median costs = 4.1 vs. 5.6 and 2.4 vs. 2.9 million JPY; P = 0.018], while they were not observed for right-sided CRC [RR = 0.88 (95% confidence interval, 0.61-1.28), mean and median costs = 4.0 vs. 4.1 and 2.7 vs. 2.9 million JPY; P = 0.995]. This study demonstrated the improved outcomes by FOBT for left-sided CRC, whereas its impact was limited for right-sided CRC.

Machine learning-based prediction model for brain metastasis in patients with extensive-stage small cell lung cancer

Brain metastases (BMs) in extensive-stage small cell lung cancer (ES-SCLC) are often associated with poor survival rates and quality of life, making the timely identification of high-risk patients for BMs in ES-SCLC crucial. Patients diagnosed with ES-SCLC between 2010 and 2018 were screened from the Surveillance, Epidemiology, and End Results (SEER) database. Four different machine learning (ML) algorithms were used to create prediction models for BMs in ES-SCLC patients. The accuracy, sensitivity, specificity, AUROC, and AUPRC were compared among these models and traditional logistic regression (LR). The random forest (RF) model demonstrated the best performance and was chosen for further analysis. The AUROC and AUPRC were calculated and compared. The findings from the RF model were utilized to identify the risk factors linked to BMs in patients diagnosed with ES-SCLC. Examining 4,716 instances of ES-SCLC, the research conducted an analysis, with brain metastases arising in 1,900 cases. Through evaluation of the ROC curve and PRC concerning the RF Model, results depicted an AUROC of 0.896 (95% CI: 0.889–0.899) and AUPRC of 0.900 (95% CI: 0.895–0.904). Test accuracy measured at 0.810 (95% CI: 0.784–0.833), sensitivity at 0.797 (95% CI: 0.756–0.841), and specificity at 0.819 (95% CI: 0.754–0.879). Based on the SHAP analysis of the RF predictive model, the top 10 most relevant features were identified and ranked in order of relative importance: bone metastasis, liver metastasis, radiation, age, tumor size, primary tumor location, N-stage, race, T-stage, and chemotherapy. The research developed and validated a predictive RF model using clinical and pathological data to predict the risk of BMs in patients with ES-SCLC. This model may assist physicians in making clinical decisions that could delay the onset of BMs and improve patient survival rates.

OGC SO21 - Role of Staging Laparoscopy on oesophageal and junctional cancer management

Abstract Background Staging laparoscopy and peritoneal cytology is currently recommended as a staging tool required for oesophageal and gastro-oesophageal junction (OGJ) adenocarcinomas. However, evidence is variable regarding the utility of this investigation, leading to heterogenous practice in the UK. With improved staging sensitivity of CT and PET imaging and inclusion of routine MDT discussion for upper GI cancer patients, staging laparoscopy may not be necessary for all patients with oesophago-gastric cancer, and in fact may delay their treatment. We thus aimed to assess the impact of staging laparoscopy on the treatment algorithm of patients with oesophago-gastric cancer. Method All staging laparoscopies undertaken between January 2022 and March 2024 were identified from our surgical database. Patients were included if they had oesophago-gastric adenocarcinoma, with a plan for curative treatment. Data collected included age, gender, location of primary tumour, CT/PET staging, laparoscopy findings, impact on treatment intention, neoadjuvant treatment, and final histology. Primary outcome was incidence of positive microscopic or macroscopic peritoneal disease for oesophageal and OGJ malignancy. Results 127 patients were identified - 69 (55%) oesophageal, 25 (20%) GOJ, and 32 (24.4%) gastric cancer. 1/70 (1.4%) patient diagnosed endoscopically with oesophageal cancer had positive peritoneal disease, which was suspected due to pre-operative imaging findings of ascites and suspicions of linitis plastica. Of patients diagnosed with GOJ cancer, 4/25 patients (16%) had peritoneal disease present. None of the 39 patients with oesophageal/junctional tumours with clinical T1-2 disease were found to have peritoneal disease on staging laparoscopy. 6/32 (19%) patients with gastric cancer were found to have unexpected peritoneal disease present. Conclusion This study found minimal impact staging laparoscopy has on the management of primary oesophageal cancers. Consideration can be made of limiting staging in oesophageal cancer to patients with suspicious findings on CT/PET imaging. For GOJ tumours, there may be a role for limiting staging laparoscopy for Siewert 1 tumours to T3/4 tumours based on CT/PET findings. Importantly, accurate identification on primary endoscopy of the location of the tumour in relation to the gastro-oesophageal junction is necessary to help guide ongoing management.

OGC SO22 - Accuracy of CT and FDG/PET clinical staging within a dedicated multidisciplinary service for patients with oesophago-gastric cancer

Abstract Background Accurate staging for oesophago-gastric cancer is important in ensuring correct treatment pathways, avoiding unnecessary surgery and providing prognostication for patients. Previously, cross sectional imaging in accurately providing tumour (T) and nodal (N) staging has been variable for upper GI malignancies, with usage of invasive investigations such as EUS to provide more specific local staging. With the increased utilisation of specialist multidisciplinary involvement and improved technology, we aimed to assess whether CT and PET imaging may be able to provide sufficiently accurate staging required for treatment decision making. Method All patients who underwent oesoophagogastric resections between January 2022 and March 2024 were identified from our surgical database. Patients were included if they had oesophago-gastric cancer, and underwent curative resection without neo-adjuvant treatment. Data collected included age, gender, location of primary tumour, CT/PET staging, and final histology. Outcomes assessed included rate of understaging in clinical and pathological T and N staging, and sensitivity and specificity of imaging in identifying presence of nodal disease. Results 38 patients were included in this analysis. For oesophageal and GOJ cancers, T stage under-reporting occurred in 6/27 (22%) patients, and N under-reporting in 7/27 (27%) patients. Radiological staging correlated with final pathological staging in 55% of T staging and 59% of N staging. Sensitivity (55.56%, 95% CI 21-86%) and specificity (72.2%, 95% CI 46.5-90.3%) for nodal disease on CT/PET was low, however no tumour or nodal under-staging would have impacted management. Gastric cancer staging accuracy assessment was limited by small numbers (n=12), however T under-staging occurred in 5/12 (42%) patients and N under-staging occurred in 5/11 patients (45%). Conclusion Involvement of dedicated radiology services in multidisciplinary care for oesophago-gastric cancer provides adequate radiological staging to guide treatment. Gastric cancer clinical staging requires laparoscopic and endoscopic assessment for accurate tumour assessment and management guidance. Radiological under-staging is less common in oesophageal and GOJ tumours than gastric cancer and has minimal impact on patient management.

Nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: Results of Polish multicenter observational study.

Patients with head and neck squamous cell carcinoma (HNSCC) who have progressed following primary treatment (PT) have a poor prognosis. In this group, nivolumab has been demonstrated to significantly improve outcomes. This study presents the efficacy of nivolumab in Polish patients with recurrent and/or metastatic (R/M) HNSCC using real-world data. The analyzed group consisted of 324 adult patients with R/M HNSCC following platinum-based therapy. Patients were divided into 3 groups based on the time from completion of PT to nivolumab initiation (tPT-N): within 6 months (refractory), between 6 and 24 months (sensitive, tPT-N ≤24), and beyond 24 months (sensitive, tPT-N >24). Survival analysis and the Cox proportional hazards model were performed to evaluate how various risk factors affect patient outcomes. The 1-year and 2-year overall survival (OS) was 19.1%, 6.1%, 30.7%, 9.4%, and 45.7%, 29.1% in refractory, sensitive tPT-N ≤24, sensitive tPT-N >24 patients, respectively and was higher for both sensitivity groups vs. refractory (p = .004) and for sensitive tPT-N >24 versus refractory and sensitive tPT-N ≤24 (p <.001). Patients with nasopharyngeal cancer had OS significantly higher than patients with other primary tumor localization. The multivariate Cox analysis showed a significant favorable effect of tPT-N >24 (HR = 0.53, p = .001) and nasopharyngeal cancer on OS (HR = 0.20, p = .008). Conversely, female sex was identified as an unfavorable factor for OS (HR = 1.48, p = .020). In our study, we established that the benefit of nivolumab increases with the increasing tPT-N. The probability of death is significantly lower in male patients and patients with nasopharyngeal cancer regardless of tPT-N.

Unscheduled Hospital Admission as a Prognostic Factor in the Oncologic Patient: A Retrospective Study.

Aims This research aimed to determine the correlation between survival, symptoms, and unscheduled admission in oncologic patients. Furthermore, this study aimed to develop a prognostic model that helps clinicians establish the indication of intervention by palliative care teams. Methodology A retrospective study of patients' digital clinical history registry was conducted to meet the two core objectives. The study population was patients with solid tumors undergoing unscheduled admissions to the oncology ward between January 1, 2018, and May 31, 2018. Demographic and clinical variables of those patients wereanalyzed. Specifically, the statistical analysis involved descriptive analysis, Kaplan-Meier curves, Log-Rank, andChi-Squared Automatic Interaction Detection decision tree modeling. Results The results were obtained from 100 admissions of patients with an average age of 64. Of the patient cases examined, 67% (n = 67) were male.In 72% (n = 72) of the cases, patients presented with Stage IV tumors, and the most frequent primary tumor location among the admissions was lung, at 29% (n = 29). Intervention by the palliative care team occurred for 38% (n = 38) of patients. Mortality at 30, 90, 180, and 365 days was 34% (n = 34), 56% (n = 56), 71% (n = 71), and 78% (n = 78), respectively. Hepatic metastasis was the main predictor of mortality at 30 days (65%, n = 13) and at 90 days (90%, n = 18). In the absence of hepatic metastasis, the presence of more than one symptom predicted a mortality rate of 70% at 30 days. The main factor associated with mortality at 180 and 365 days was the tumor stage, with stage IV tumors having the highest mortality rate (84.7%, n = 61, and 90.3%, n = 65, respectively). Among the Stage IV population, the primary site shows a significant impact on survival, with colorectal/reproductive tumors being associated with decreased mortality. Conclusion Unscheduled admission is a negative prognostic factor in oncologic patients. An unscheduled admission can be expected to result in low survival in an oncologic patient, especially in those presenting with stage IV; involving non-colorectal/reproductive primaries; or presenting with pain, dyspnea, cachexia, or delirium.

Atezolizumab Plus Chemotherapy With or Without Bevacizumab in Advanced Biliary Tract Cancer: Clinical and Biomarker Data From the Randomized Phase II IMbrave151 Trial.

Biliary tract cancers (BTCs) harbor an immunosuppressed tumor microenvironment and respond poorly to PD-1/PD-L1 inhibitors. Bevacizumab (anti-vascular endothelial growth factor) plus chemotherapy can promote anticancer immunity, augmenting response to PD-L1 inhibition. This randomized, double-blind, proof-of-concept phase II study enrolled patients (n = 162) with previously untreated advanced BTC (IMbrave151; ClinicalTrials.gov identifier: NCT04677504). Patients were randomly assigned 1:1 to receive cycles of atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) or atezolizumab plus placebo once every 3 weeks until disease progression or unacceptable toxicity. All patients received cisplatin (25 mg/m2) plus gemcitabine (1,000 mg/m2; cisplatin plus gemcitabine [CisGem]) on days 1 and 8 once every 3 weeks for up to eight cycles. Stratification of patients was by disease status, geographic region, and primary tumor location. The primary end point was progression-free survival (PFS). No formal hypothesis testing was performed. Exploratory correlative biomarker analysis was undertaken using transcriptome analysis (n = 95) and mutation profiling (n = 102) on baseline tumor samples. Between February and September 2021, 162 patients were enrolled. Median PFS was 8.3 months in the bevacizumab arm and 7.9 months in the placebo arm (stratified hazard ratio [HR], 0.67 [95% CI, 0.46 to 0.95]). Median overall survival (OS) was 14.9 and 14.6 months in the bevacizumab and placebo arms, respectively (stratified HR, 0.97 [95% CI, 0.64 to 1.47]). The incidence of grade 3 or 4 adverse events was 74% in both arms. High VEGFA gene expression was associated with improved PFS (HR, 0.44 [95% CI, 0.23 to 0.83]) in the bevacizumab arm versus placebo. In unselected patients with advanced BTC, adding bevacizumab to atezolizumab plus CisGem modestly improves PFS but not OS. High VEGFA gene expression may represent a predictive biomarker of benefit from atezolizumab/bevacizumab, warranting further investigation.

The Prognostication of Surgically Resected Head and Neck Squamous Cell Carcinoma Using Pre-Therapy Neutrophil and Lymphocyte Counts.

Hematological markers, such as neutrophils (ANC), lymphocyte (ALC), and neutrophil-lymphocyte ratio (NLR), may serve as indicators of systemic inflammation and immune response in head and neck squamous cell carcinoma (HNSCC). However, their prognostic significance across HNSCC subtypes remains to be fully elucidated. We conducted a secondary analysis of a randomized clinical trial involving patients with surgically resected HNSCC with either positive margins or extranodal extension. These patients received either adjuvant chemoradiation with or without lapatinib. We explored the correlation between pre-therapy ANC, ALC, and NLR levels and overall survival (OS) as well as disease-free survival (DFS). A sub-group analysis examined potential links between these markers, primary tumor location, and HPV status. Of the 688 patients in the trial, we included 681 patients with documented pre-therapy ANC and ALC values. High pre-therapy ANC and ALC were significantly associated with reduced OS (HR, 1.56; 95% CI: 1.19-2.05) and (HR, 1.34; 95% CI: 1.01-1.79), respectively. High NLR did not significantly affect OS (HR, 1.09; 95% CI: 0.81-1.47). Subgroup analysis indicated significantly reduced OS in patients with high ANC across oropharyngeal, non-oropharyngeal, and HPV-negative subtypes. High ANC, ALC, and NLR did not impact DFS notably. Elevated pre-therapy ANC is strongly associated with decreased survival across all patients and subgroups, ALC was only significant in the general patient analysis. NLR's association with reduced OS was not statistically significant. These biomarkers may provide greater prognostic value in patients with oropharyngeal cancer and seemed to be more strongly associated with OS than DFS. Clinicaltrials.gov identifier: NCT00424255; URL: https://clinicaltrials.gov/ct2/show/study/NCT00424255.

Uncovering factors predicting BRAF mutation in cutaneous melanoma

Abstract Introduction/Objective BRAF mutations are considered to be the most common genetic alteration in cutaneous melanoma (CM). Patient management relies on assessing molecular biomarkers enabling the personalization of patients’ treatment. The goal of this study was to develop the tools for predicting BRAF mutation using routine clinical and histological features. Methods/Case Report A total of 2041 CM cases were enrolled in the study to identify factors associated with BRAF mutation. Variables included sex, age, primary location, stage, histological type, ulceration, mitosis, Clark level, Breslow thickness, lymphocytes, lymphovascular invasion (LVI), perineural invasion (PNI), regression, microsatellite, association with nevus. Results (if a Case Study enter NA) The Ukrainian population demonstrated a high rate of BRAF mutation in CM, associated with the younger age and location at non-sun-expose skin. This study also revealed gender-specific differences in CM anatomic distribution and BRAF mutation subtype prevalence. By using the genetic selection method, the minimal set of variables related to BRAF mutations was defined and included age, primary tumor location, histological type, ulceration, LVI, and association with nevus. To encounter non- linear links, the non-linear neural network modeling was applied. For this aim multilayer perceptron (MLP) with one hidden layer was used. The hidden layer architecture included 4 neurons with a logistic activating function. The AUROCMLP6 of the model was 0.79 (0.74 – 0.84). When applying the optimal threshold, the following characteristics of the model were reached: sensitivity - 89.4% (84.5 – 93.1%); specificity - 50.7% (42.2% – 59.1%); positive predictive value (PPV) - 73.1% (69.6% – 76.3%) and NPV - 76.0% (67.6% – 82.8%) respectively. The developed MLP model allows the prediction of BRAF status in CM, facilitating decisions concerning further patient management. Conclusion The developed MLP model, relying on 6 variables analysis allows the prediction of BRAF status in melanoma, facilitating decisions concerning further patient management.

First-Line Therapy in Metastatic, RAS Wild-Type, Left-Sided Colorectal Cancer: Should Everyone Receive Anti-EGFR Therapy?

This narrative review explores the efficacy and applicability of anti-EGFR therapy as the first-line treatment for patients with RAS wild-type (WT) left-sided metastatic colorectal cancer (mCRC). It critically examines current guidelines, along with recent evidence in the literature, to assess whether it should be universally applied. Recent evidences highlight the variability of the response to anti-EGFR therapies due to molecular diversity and several clinical factors, such as RAS mutational status and primary tumor location. Anti-EGFR plus chemotherapy is the standard first-line treatment for most patients with MSS, RAS-WT, left-sided mCRC. Whether this combination is the best treatment for these patients remains an open question. This review delves into the role of EGFR inhibition in mCRC, focusing on clinical factors and the knowledge of biology, molecular targets, and biomarkers. It underscores the crucial role of a personalized approach, empowering healthcare providers and equipping them with the confidence to make informed decisions.